A FAMILY OF TRANSMEMBRANE PROTEINS WITH HOMOLOGY TO THE MET-HEPATOCYTE GROWTH-FACTOR RECEPTOR

In hunting for unknown genes on the human X chromosome, we identified a cDNA in Xq28 encoding a transmembrane protein (SEX) of 1871 amino ac ids, SEX shares significant homology with the extracellular domain of the receptors encoded by the oncogenes MET, RON, and SEA [hepatocyte g rowth factor (HGF) receptor family], Further screenings of cDNA librar ies identified three additional sequences closely related to SEX; thes e were named SEP, OCT, and NOV and were located on human chromosomes 3 p, 1, and 3q, respectively, The proteins encoded by these genes contai n large cytoplasmic domains characterized by a distinctive highly cons erved sequence (SEX domain), Northern blot analysis revealed different expression of the SEX family of genes in fetal tissues, with SEX, OCT , and NOV predominantly expressed in brain, and SEP expressed at highe st levels in kidney, In situ hybridization analysis revealed that SEX has a distinctive pattern of expression in the developing nervous syst em of the mouse, where it is found in postmitotic neurons from the fir st stages of neuronal differentiation (9.5 day postcoitus), The SEX pr otein (220 kDa) is glycosylated and exposed at the cell surface, Unlik e the receptors of the HGF family, p220(SEX), a MET-SEX chimera or a c onstitutively dimerized TPR-SEX does not show tyrosine kinase activity , These data define a gene family (SEX family) involved in the develop ment of neural and epithelial tissues, which encodes putative receptor s with unexpected enzymatic or binding properties.